Comparison of HTK-Custodiol and St-Thomas solution as cardiac preservation solutions on early and midterm outcomes following heart transplantation.

OBJECTIVES: The choice of the cardiac preservation solution for myocardial protection at time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm heart transplantation (HTx) outcomes. We retrospectively compared our adult HTx performed with 2 different solutions, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. METHODS: From January 2009 to December 2020, 154 consecutive HTx of adult patients, followed up in pre- and post-transplantation by 2 different tertiary centres, were performed at the University Hospital of Lausanne, Switzerland. From 2009 to 2015, the cardiac preservation solution used was exclusively St-Thomas, whereafter an institutional decision was made to use HTK-Custodiol only. Patients were classified in 2 groups accordingly. RESULTS: There were 75 patients in the St-Thomas group and 79 patients in the HTK-Custodiol group. The 2 groups were comparable in terms of preoperative and intraoperative characteristics. Postoperatively, compared to the St-Thomas group, the Custodiol group patients showed significantly lower inotropic scores [median (interquartile range): 35.7 (17.5-60.2) vs 71.8 (31.8-127), P < 0.001], rejection scores [0.08 (0.0-0.25) vs 0.14 (0.05-0.5), P = 0.036] and 30-day mortality rate (2.5% vs 14.7%, P = 0.007) even after adjusting for potential confounders. Microscopic analysis of the endomyocardial biopsies also showed less specific histological features of subendothelial ischaemia (3.8% vs 17.3%, P = 0.006). There was no difference in primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation. The use of HTK-Custodiol solution significantly improved midterm survival (Custodiol versus St-Thomas: hazard ratio = 0.20, 95% confidence interval: 0.069-0.60, P = 0.004). CONCLUSIONS: This retrospective study comparing St-Thomas solution and HTK-Custodiol as myocardial protection during heart procurement showed that Custodiol improves outcomes after HTx, including postoperative inotropic score, rejection score, 30-day mortality and midterm survival.

[Cardiology: what's new in 2023]. / Cardiologie: ce qui a changé en 2023.

The year 2023 has been extremely rich in new publications in the various subfields of cardiology. Furthermore, the European Society of Cardiology (ESC) has issued revised guidelines focused on the management of acute coronary syndrome (ACS) and endocarditis, as well as an update on the recommendations for the management of heart failure and cardiovascular prevention. The most significant updates according to the Cardiology Department of CHUV are summarized in this review article.

L'année 2023 a été extrêmement riche en nouvelles publications dans les différents sous-domaines de la cardiologie. De plus, la Société européenne de cardiologie (ESC) a formulé des directives révisées axées sur le management du syndrome coronarien aigu (SCA) et de l'endocardite ainsi qu'une mise à jour des recommandations sur la prise en charge de l'insuffisance cardiaque et la prévention cardiovasculaire. Les nouveautés les plus importantes selon l'équipe du Service de cardiologie du CHUV sont résumées dans cet article de synthèse.

Pressure Overload and Right Ventricular Failure: From Pathophysiology to Treatment.

Right ventricular failure (RVF) is often caused by increased afterload and disrupted coupling between the right ventricle (RV) and the pulmonary arteries (PAs). After a phase of adaptive hypertrophy, pressure-overloaded RVs evolve towards maladaptive hypertrophy and finally ventricular dilatation, with reduced stroke volume and systemic congestion. In this article, we review the concept of RV-PA coupling, which depicts the interaction between RV contractility and afterload, as well as the invasive and non-invasive techniques for its assessment. The current principles of RVF management based on pathophysiology and underlying etiology are subsequently discussed. Treatment strategies remain a challenge and range from fluid management and afterload reduction in moderate RVF to vasopressor therapy, inotropic support and, occasionally, mechanical circulatory support in severe RVF.

Risk Stratification in Pulmonary Arterial Hypertension, Update and Perspectives.

Risk stratification in pulmonary arterial hypertension (PAH) is crucial in assessing patient prognosis. It serves a prominent role in everyday patient care and can be determined using several validated risk assessment scores worldwide. The recently published 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines underline the importance of risk stratification not only at baseline but also during follow-up. Achieving a low-risk status has now become the therapeutic goal, emphasising the importance of personalised therapy. The application of these guidelines is also important in determining the timing for lung transplantation referral. In this review, we summarise the most relevant prognostic factors of PAH as well as the parameters used in PAH risk scores and their evolution in the guidelines over the last decade. Finally, we describe the central role that risk stratification plays in the current guidelines not only in European countries but also in Asian countries.

Pulmonary Hypertension in Left Heart Diseases: Pathophysiology, Hemodynamic Assessment and Therapeutic Management.

Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive backward transmission of elevated left heart pressures in the setting of heart failure, either with preserved (HFpEF) or reduced (HFrEF) ejection fraction, which increases the pulsatile afterload of the right ventricle (RV) by reducing pulmonary artery (PA) compliance. In a subset of patients, progressive remodeling of the pulmonary circulation resulted in a pre-capillary phenotype of PH, with elevated pulmonary vascular resistance (PVR) further increasing the RV afterload, eventually leading to RV-PA uncoupling and RV failure. The primary therapeutic objective in PH-LHD is to reduce left-sided pressures through the appropriate use of diuretics and guideline-directed medical therapies for heart failure. When pulmonary vascular remodeling is established, targeted therapies aiming to reduce PVR are theoretically appealing. So far, such targeted therapies have mostly failed to show significant positive effects in patients with PH-LHD, in contrast to their proven efficacy in other forms of pre-capillary PH. Whether such therapies may benefit some specific subgroups of patients (HFrEF, HFpEF) with specific hemodynamic phenotypes (post- or pre-capillary PH) and various degrees of RV dysfunction still needs to be addressed.

Caplacizumab for treating subacute intra-stent thrombus occurring despite efficacious double anti-platelet treatment and anticoagulation: a case report.

Background: Acute and subacute stent thromboses are a rare complication associated with high mortality and morbidity occurring in ∼1.5% of patients treated with primary percutaneous intervention for ST-elevation myocardial infarction (STEMI). Recent publications describe a potential role of the von Willebrand factor (VWF) in thrombus formation at sites of critical coronary stenosis in STEMI. Case summary: We describe a 58-year-old woman with STEMI at initial presentation, who suffered subacute stent thrombosis despite good stent expansion, efficacious dual antiplatelet therapy, and therapeutic anticoagulation. Because of very high VWF values, we administered N-acetylcysteine in order to depolymerize VWF, but the drug was not well tolerated. Since the patient was still symptomatic, we used caplacizumab in order to prevent VWF from interacting with platelets. Under this treatment, the clinical and angiographic course was favourable. Discussion: Considering a modern view of intracoronary thrombus pathophysiology, we describe an innovative treatment approach, which eventually ended in a favourable outcome.

Case report: Disseminated Scedosporium apiospermum infection with invasive right atrial mass in a heart transplant patient.

Scedosporium apiospermum associated endocarditis is extremely rare. We report a case of a disseminated S. apiospermum infection with an invasive right atrial mass in a 52-year-old male, 11 months after heart transplantation, referred to our institution for an endogenous endophthalmitis with a one-month history of diffuse myalgias and fatigue. The patient had been supported two times with extracorporeal membrane oxygenation (ECMO) during the first three postoperative months. The echocardiography on admission revealed a mass in the right atrium attached to a thickened lateral wall. The whole-body [18F]FDG PET/CT revealed systemic dissemination in the lungs, muscles, and subcutaneous tissue. Blood cultures were positive on day three for filamentous fungi later identified as S. apiospermum. The disease was refractory to a 3-week dual antifungal therapy with voriconazole and anidulafungin in addition to reduced immunosuppression, and palliative care was implemented.

Cardiac Surgery in Advanced Heart Failure.

Mechanical circulatory support and heart transplantation are established surgical options for treatment of advanced heart failure. Since the prevalence of advanced heart failure is progressively increasing, there is a clear need to treat more patients with mechanical circulatory support and to increase the number of heart transplantations. This narrative review summarizes recent progress in surgical treatment options of advanced heart failure and proposes an algorithm for treatment of the advanced heart failure patient at >65 years of age.

Comparison of Risk Stratification Scores in Pulmonary Arterial Hypertension: A Monocentric Retrospective Study at Lausanne University Hospital.

BACKGROUND: Risk assessment is the cornerstone of pulmonary arterial hypertension (PAH) management. Risk stratification scores predict prognosis and help individualize treatment. OBJECTIVES: The aims of the study include the following: (1) to compare the prediction for transplant-free survival (TFs) of 3 risk assessment tools at 3 and 5 years after diagnosis and (2) to analyze whether the initial risk stratification was altered after 1 year of treatment. METHOD: We collected retrospectively data of 50 patients diagnosed with PAH Group 1. We categorized them as low, intermediate, and high mortality risk at baseline and at 1 year with the (1) Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score version 2.0, (2) Swedish/Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (PH) (COMPERA) score, and (3) French PH Network Registry (FPHR) score. RESULTS: TFs at 3 years is predicted by the 3 scores computed at baseline with an area under the curve (AUC) of 0.73, 0.73, and 0.77, respectively. The predictive value increased when the scores were calculated after 1 year of treatment (AUC = 0.91, 0.89, and 0.78). The prediction of TFs at 5 years was better evaluated by the COMPERA and FPHR (AUC = 0.85) than by REVEAL 2.0 (AUC = 0.69) computed at baseline. A low risk status was associated with excellent TFs whatever the scoring used. CONCLUSION: In accordance with the original publications, the 3 scores are able to predict survival up to 5 years after diagnosis. The better performance of the scores after 1 year is a further evidence for their clinical use and an indirect proof for treatment efficacy.

Complement blockade with eculizumab to treat acute symptomatic humoral rejection after heart transplantation.

Antibody-mediated rejection (AMR) is a major barrier preventing successful discordant organ xenotransplantation, but it also occurs in allotransplantation due to anti-HLA antibodies. Symptomatic acute AMR is rare after heart allograft but carries a high risk of mortality, especially >1 year after transplant. As complement activation may play a major role in mediating tissue injury in acute AMR, drugs blocking the terminal complement cascade like eculizumab may be useful, particularly since "standards of care" like plasmapheresis are not based on strong evidence. Eculizumab was successfully used to treat early acute kidney AMR, a typical condition of "active AMR," but showed mitigated results in late AMR, where "chronic active" lesions are more prevalent. Here, we report the case of a heart recipient who presented with acute heart failure due to late acute AMR with eight de novo donor-specific anti-HLA antibodies (DSA), and who fully recovered allograft function and completely cleared DSA following plasmapheresis-free upfront eculizumab administration in addition to thymoglobulin, intravenous immunoglobulins (IVIG), and rituximab. Several clinical (acute onset, abrupt and severe loss of graft function), biological (sudden high-level production of DSA), and pathological features (microvascular injury, C4d deposits) of this cardiac recipient are shared with early kidney AMR and may indicate a strong role of complement in the pathogenesis of acute graft injury that may respond to drugs like eculizumab. Terminal complement blockade should be further explored to treat acute AMR in recipients of heart allografts and possibly also in recipients of discordant xenografts in the future.

Has the profile of heart transplantation recipients changed within the last three decades?

BACKGROUND: Heart transplantation remains the most durable treatment for patients with end-stage heart failure refractory to medical treatment. Central elements of the listing criteria for heart transplantation have remained largely unchanged in the last three decades whereas treatment of heart failure has significantly increased survival and reduced disease-related symptoms. It remains unknown whether the improvement of heart failure therapy changed the profile of heart transplantation candidates or affected post-transplant survival. METHODS: The study investigated a total of 323 heart transplant recipients of the Lausanne University Hospital with 328 transplant operations between 1987 and 2018. Patients were separated into three groups on the basis of availability of heart failure therapy: period 1 (1987-1998; n = 115) when renin-angiotensin system blockade and diuretic treatment were available; period 2 (1999-2010; n = 106) marked by the addition of beta-blocker and mineralocorticoid receptor antagonist treatment in severe heart failure, and the establishment of cardiac defibrillator and resynchronisation therapy; period 3 (2011-2018; n = 107) characterised by the increasing use of ventricular assist devices for bridge to transplantation. RESULTS: The patient characteristics age (all: 53.4 years), male sex (all: 79%) and body mass index (all: 24.5 kg/m2) did not differ between periods. History of arterial hypertension was less prevalent in period 2 (period 1 vs 2 vs 3: 44 vs 28 vs 43%, p = 0.04) whereas other cardiovascular risk factors were equally distributed. Left ventricular ejection fraction, VO2max, and pulmonary vascular resistance were not different between the three periods. The prevalence of ischaemic cardiomyopathy was higher in periods 1 and 3; dilated non-ischaemic cardiomyopathy was more frequent in period 2. Post-transplant 1-year survival was highest in period 3 (1 vs 2 vs 3: 87.2 ± 3.2% vs 70.8 ± 4.4% vs 93.0 ± 2.6%, p always ≤0.02), and the Kaplan-Meier estimates of survivors of the first year post-transplant were not different between the three periods. In descriptive analysis, early mortality was not associated with acknowledged pretransplant predictors of post-transplant mortality. CONCLUSION: Availability of different medical heart failure treatments did not result in greatly different pretransplant characteristics of heart transplantation recipients across the three periods. This suggests that the maintained central criteria of listing for heart transplantation still identify end-stage heart failure patients with a similar profile. This finding can explain the unchanged overall mortality on condition of 1-year survival across the three periods, since pretransplant characteristics are relevant for long-term survival after heart transplantation.

IgA Vasculitis With Henoch-Schönlein Purpura as an Immune Complication Associated With Left Ventricle Assist Device Insertion.

The implantation of left ventricular assist devices (LVADs) in patients with end-stage heart failure can be associated with some forms of immune dysregulation and systemic inflammatory response. These abnormalities may be related to impaired T-lymphocyte-dependent immunity and B-lymphocyte hyper-reactivity and may lead to the development of autoimmune processes and the occurrence of severe infections. We present here the first observation of a peculiar immune complication associated with the implantation of an LVAD, characterized by an IgA vasculitis clinically manifested as Henoch-Schönlein purpura. The vasculitis was biologically associated with a significant increase of the plasma levels of C-X-C motif chemokine ligand (CXCL)13, a CXC motif chemokine produced by follicular dendritic cells, which targets CXCR5, a receptor primarily expressed by B lymphocytes, to promote their chemotaxis and expansion. Spontaneous resolution of the vasculitis occurred over time, concomitantly to a decrease of CXCL13 expression. These findings suggest that CXCL13 might be an interesting biomarker to detect auto-antigen sampling and the risk of secondary immune complications following LVAD implantation.

Body composition and maximal exercise capacity after heart transplantation.

AIMS: Maximal exercise capacity as measured by peak oxygen consumption (pVO2 ) in cardiopulmonary exercise testing (CPET) of heart transplant recipients (HTR) is limited to a 50-70% level of healthy age-matched controls. This study investigated the relationship between body composition and pVO2 during the first decade post-transplant. METHODS AND RESULTS: Body composition was determined by dual-energy X-ray absorptiometry (DXA) and pVO2 by CPET in 48 HTR (n = 38 males; mean age 51 ± 12 years). A total of 95 assessments were acquired 1-9 years post-transplant, and the results of four consecutive periods were compared [Period 1: 1-2 years (n = 25); 2: 3-4 years (n = 23); 3: 5-6 years (n = 23); 4: 7-9 years (n = 24)]. Linear regression analysis analysed the correlation between pVO2 and pairs of appendicular lean mass (ALM) and fat mass (FM). The relation between ALM and daily dose of calcineurin inhibitor (CNI) was explored using partial correlation controlling for age, gender, and height. pVO2 increased from 0.98 (0.34) to 1.35 (0.35) L/min (P < 0.01) between Periods 1 and 4 corresponding to 54.5-63.3% of predicted value. Peak heart rate (HR) raised from 115 ± 19 to 131 ± 23 b.p.m. (P = 0.05), and anaerobic threshold (AT = VO2 achieved at AT) increased from 0.57 (0.18) to 0.83 (0.35) L/min (P < 0.01) between Periods 1 and 3. Median FM normalized to height2 (FMI) always remained elevated (>8.8 kg/m2 ). ALM normalized to body mass index increased from 0.690 (0.188) to 0.848 (0.204) m2 (P = 0.02) between Periods 1 and 4, explaining 45% of the variance of pVO2 (R2  = 0.455; P < 0.001). Eighty-one per cent of the variance of pVO2 (R2  = 0.817; P < 0.001) in multiple regression was explained by AT (ß = 0.488), ALM (ß = 0.396), peak HR (ß = 0.366), and FMI (ß = -0.181). ALM was negatively correlated with daily CNI dose (partial R = -0.258; P = 0.01). CONCLUSIONS: After heart transplantation, the beneficial effect of peripheral skeletal muscle gain on pVO2 is opposed by increased FM. Our findings support lifestyle efforts to fight adiposity and CNI dose reduction in the chronic stable phase to favour positive adaptation of peripheral muscle mass.

Two-dimensional transthoracic echocardiography at rest for the diagnosis, screening and management of pulmonary hypertension.

Doppler echocardiography is widely used in everyday clinical practice for the detection of pulmonary hypertension (PH) in symptomatic patients and in populations particularly at risk of pulmonary arterial hypertension (PAH). It allows accurate estimation of systolic pulmonary arterial pressure but may lack precision in particular situations. In addition, echocardiography can help to distinguish between pre- and post-capillary PH and is a very good tool to evaluate right ventricular systolic function, which is of great prognostic interest in PAH. This article reviews the current knowledge about methodologic aspects of assessing pulmonary pressure and PH origin by echo, including a discussion about abnormal thresholds. It also details advanced techniques like right ventricular strain imaging and new concepts like right ventricle – pulmonary artery coupling evaluation that have become “matured” enough to be definitely brought to routine evaluation.

[Practical considerations in the use of SGLT2 inhibitors in cardiovascular diseases]. / Considérations pratiques pour l'utilisation des inhibiteurs du SGLT2 dans les maladies cardiovasculaires.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs which offer cardiovascular (CV) and renal benefits. They are currently indicated as first-line treatments of type 2 diabetes mellitus (T2DM) in patients with CV disease, high CV risk, renal disease, or heart failure with reduced ejection fraction (HFrEF). Two randomized clinical trials have shown the benefits of dapagliflozin and empagliflozin in patients with HFrEF, regardless of the presence of T2DM. Despite an overall favorable safety profile, attention has to be paid to adverse events, such as an increased risk of euglycemic diabetic ketoacidosis and genital mycotic infections. We present an up-to-date narrative literature review of the physiological mechanisms of action, current indications, and side effects of SGLT2 inhibitors.

Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) sont une classe d'antidiabétiques oraux ayant de nombreux bénéfices cardiovasculaires (CV) et rénaux. Ils sont indiqués chez les patients avec un diabète de type 2 (DT2) et une maladie CV, un risque CV élevé, une insuffisance rénale chronique ou une insuffisance cardiaque à fraction d'éjection réduite (ICFER). Des essais cliniques randomisés ont montré les bénéfices de la dapagliflozine et de l'empagliflozine chez les patients avec une ICFER, avec ou sans DT2. Malgré un profil de sécurité favorable, il convient de connaître les effets indésirables éventuels, tels que l'acidocétose euglycémique et les infections génito-urinaires. Nous présentons une revue narrative de la littérature à jour portant sur les mécanismes d'action, indications et effets secondaires des iSGLT2.

Simple equations to predict the effects of veno-venous ECMO in decompensated Eisenmenger syndrome.

Adult patients with uncorrected congenital heart diseases and chronic intracardiac shunt may develop Eisenmenger syndrome (ES) due to progressive increase of pulmonary vascular resistance, with significant morbidity and mortality. Acute decompensation of ES in conditions promoting a further increase of pulmonary vascular resistance, such as pulmonary embolism or pneumonia, can precipitate major arterial hypoxia and death. In such conditions, increasing systemic oxygenation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) could be life-saving, serving as a bridge to treat a potential reversible cause for the decompensation, or to urgent lung transplantation. Anticipating the effects of VV-ECMO in this setting could ease the clinical decision to initiate such therapeutic strategy. Here, we present a series of equations to accurately predict the effects of VV-ECMO on arterial oxygenation in ES and illustrate this point by a case of ES decompensation with refractory hypoxaemia consecutive to an acute respiratory failure due to viral pneumonia.